The Tuberculosis Research Unit contract is part of NIAID's response to the global resurgence of tuberculosis (TB). The major elements of its Statement of Work include: 1) Develop and implement a systematic approach towards furthering scientific understanding of the epidemiology of TB in populations with a high prevalence of disease; 2) Conduct coordinated, multi-disciplinary investigations of human host immunologic response mechanisms to M. tuberculosis in order to identify and validate surrogate markers for clinical use; 3) Conduct an investigation of the microbial factors expressed during various stages of M. tuberculosis infection and illness to identify surrogate markers for ultimate use in clinical trials of novel therapeutic and prevention strategies for TB; 4) Conduct human studies of potential interventions such as new vaccines, prophylactic or therapeutic regimens, using developed candidate surrogate markers of M. tuberculosis infection, TB progression and/or host protection to evaluate the validity of using these markers in future clinical trials and the safety and efficacy of new regimens; and 5) Establish and/or maintain a repository of clinical samples, including but not limited to sera and sputa from patients involved in clinical trials supported by the TBRU, and human tissue samples from well-characterized TB patients and controls, where feasible and appropriate, and distribute these specimens to qualified investigators, with approval of the Project Officer. The TBRU maintains clinical research sites in the United States, Brazil and Uganda.